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Before the war, Kansas was home to several military installations and a large Nuka-Cola factory in Newton. Some time after the conflict, a major faction in the Kansas area was the technology-worshiping Reaver cult, based in Newton.

After the fall of the Master in the far west, a great migration of super mutants he created began. They traveled east to find themselves a new home, until they found a crashed Brotherhood of Steel zeppelin, which was a part of an Air Convoy that was meant to find and destroy the remains of Master's Army. Brotherhood Paladin Latham duelled the mutant's leader, Gammorin and won. As unlikely it may seem, Latham took his opponent's name and became the new leader of the mutant army, setting up the base known as Osceolla near the airship crash site.

Around 2197 and 2198, Kansas found itself in the middle of a war zone. Several towns, mostly pre-War centers of industry, including the inhabited Great Bend, and others like Scott City and Canyon City were taken over by Calculator's robots from Vault 0. It didn't go unnoticed by Latham/Gammorin, whose mutants started actively fighting the mechanical threat.

In the meantime, the Vault 0 robots progressed east and one humanoid robot even strayed to the area of Junction City, which, unlike most other towns of that region, still maintained independence from the Brotherhood. However, when the Reaver cult tried to take the robot parts from the city's inhabitants, they were forced to ask the Brotherhood for help. Soon, the Reavers themselves had to ask the Brotherhood for help after their main camp in Newton was taken by the robots.

Around that time, the super mutant camp in the area of St. Louis, Missouri was taken by surprise by an Eastern Brotherhood of Steel squad. As the Brotherhood was unaware of the robot menace, they perceived the super mutants as a major threat and attacked them immediately. The mutant High Inquisitor Toccomatta took Simon Barnaky, the leader of the Brotherhood prisoner in St. Louis, and managed to escape the following Brotherhood assault that destroyed the mutant forces in that area. The Eastern Brotherhood also destroyed Gammorin's laboratory in Jefferson, Missouri and prevented the mutants from obtaining the nuclear missile worshiped by the ghouls in Kansas City. Eventually, even the main mutant base in Osceolla was taken and Gammorin was killed, and the remaining mutants were either taken to labor camps or drafted into Brotherhood forces.